Heterogeneous enantioselective separation and chiral sensing are of high significance in multidisciplinary scientific and technological research. Chirality plays an indispensible role in the molecular design of naturally occurring materials like proteins and DNA. Imparting homochirality is absolutely essential in these biopolymers for producing precisely defined three dimensional structures having multifunctional properties. Homochiral materials with three dimensional structures can function as biomimetic materials, chiral sensors, chiral catalysts and bioactive chiral drugs. Among the various applications of homochiral materials, chirality sensing and enantioselective separation remains a significant challenge in multidisciplinary scientific research since the biological and chemical activities are highly specific for particular chiral form. Employment of chromogenic receptors with inbuilt chirality can act as chiral sensing probes via non-covalent interactions with chiral analytes that enables the analysis of multiple components in a less time consuming manner. For example, supramolecular ensembles, ‘indicative displacement assays’, stereodynamic probes etc have been reported for chiral sensing based on coordinative complexation with chiral analytes.
Recently, an achiral supramolecular-dye ensemble probe was reported for chiral sensing of amino acids, which could be extended to proteins also.
Conjugated polymers find an inevitable place in the field of fluorimetric sensing applications. Synthesis of homochiral conjugated polymers can be achieved by polymerizing chiral monomers, doping, or blending a chiral moiety to the conjugated backbone. Chiral polyaniline with helical morphology can be achieved by doping campor sulphonic acid (- CSA) to polyaniline. So far, chiral polyaniline is the only known conjugated polymer that has been exploited for enantioselective sensing application. However, in that particular example, the racemic mixture also exhibited response which was only marginally lower than the enantiomers.
Enantiomeric excess determination and enantioselective separation of racemic mixtures are the other important aspects that still rely on tedious asymmetric synthesis involving chiral catalysts and chromatographic techniques. Homochiral metal organic frameworks have been demonstrated for enantioselective separation taking into advantage their inherent molecular adsorption property. However, it is difficult to grow homochiral metal organic framework and narrow range of analyte window are prevailing limitations. Homochiral polymers have also been applied for the kinetic resolution of racemic mixture, but stringent control on molecular weight of the polymer is very important for obtaining appreciable enantiomeric excess. The single homochiral probe for combined operations of enantioselective separation and chirality sensing for wide range of analytes is unprecedented so far.
Great Britain Pat. No. 2233248 discloses enantiomer enrichment by membrane processes. A continuous membrane adsorption/desorption or permeation process is provided which involves the enrichment/separation of enantiomers from racemic mixtures. Suitable membranes used are of essentially chiral polymers, such as optionally chemically modified chiral polysaccharides or chiral acrylic polymers. The process is effected by the selective interaction between the chirality centers of the polymer membrane and the enantiomers, and further by transmembrane concentration and pressure differences. The process can be used for the treatment of any racemic mixtures and leads to high rates of enrichment/separation of the optical isomers.
U.S. Pat. No. 5,541,342 discloses a process for separating a selected amino acid (enantiomer) from a mixture of different compounds including other amino acids is disclosed, in which process the mixture is contacted with a polymer material which is composed of cross-linked, amino-acid-based monomer units, said polymer material containing a molecular print of the selected amino acid. In the molecular print there is also bound a diastereomeric complex between the selected amino acid (enantiomer), a divalent metallic ion and the amino-acid-based monomer unit. Also the amino-acid-based monomer unit and a process for preparation thereof, as well as a polymer material composed of the amino-acid-based monomer unit and a process for the preparation thereof are disclosed.
US Pat. Appl. No. 2009072712 discloses improvement of organic electronic devices, especially electroluminescent devices, by using compounds that can comprise several isomers. One of said isomers is an excessive isomer. Organic electronic devices comprising cathode, anode and at least one layer containing at least one organic compound which comprises atropisomeric and is thus capable of the formation of diastereomers, characterized in that an atropisomeric excess of at least 10% is present.
Article titled “A homochiral metal-organic porous material for enantioselective separation and catalysis” by Jung Soo Seo et al. published in Nature, 2000, 404, 982-986 reports the synthesis of a homochiral metal-organic porous material that allows the enantioselective inclusion of metal complexes in its pores and catalyses a transesterification reaction in an enantioselective manner. Synthesis strategy, which uses enantiopure metal-organic clusters as secondary building blocks, should be readily applicable to chemically modified cluster components and thus provide access to a wide range of porous organic materials suitable for enantioselective separation and catalysis.
Article titled “Enantioselective separation using chiral mesoporous spherical silica prepared by templating of chiral block copolymers.” by Paik P et al. published in ACS Applied Materials & Interfaces, 2009;1(8):1834-42 reports synthesized chiral mesoporous silica (CMS) spheres, which can be used as a potential candidate for chiral separation. The CMS spheres with controllable pore sizes (of 2-3 nm) and high surface areas of ca. 614 m2 g-1 were synthesized by chiral templating with chiral block copolymers based on poly(ethylene oxide) and dl-glutamic acid [PEO(113)-b-(GluA)(10)]. The ordered structure of the chiral mesopores was characterized by high-resolution transmission electron microscopy, and the average pore diameters of chiral mesopores were estimated from the nitrogen adsorption-desorption measurements. The enantioselectivity properties and chiral resolution kinetics of the mesopores of silica spheres, after extraction of chiral polymers of PEO(113)-b-(1/d-GluA)(10), were scrutinized using a racemic solution of valine and measuring the circular dichroism and optical polarimetery. A chiral selectivity factor of 5.22 was found with a specific enantiomer of valine adsorbed preferably. These results raise the new possibilities of CMS spheres for enantiomeric separation and other enantioselective applications.
Article titled “Synthesis and self-assembly of rod-rod hybrid poly(γ-benzyl 1-glutamate) -block-polyisocyanide copolymers” by Alexander Kros et al. published in Angewandte Chemie, 2005, 44(28), pp 4349-4352 reports synthesis and self-assembly of rod-od hybrid poly(γ-benzyl 1-glutamate)-block-polyisocyanide copolymers. the synthesis and self-assembly of hybrid block copolymers composed of a poly(g-benzyl lglutamate) block (PBLG) and two different polyisocyanide blocks, namely, poly((S)-( )-amethylbenzylisocyanide) (PMBI) and poly(lisocyanoalanyl-1-alanine methyl ester) (1,1PIAA).
Article titled “Surface-Grafted conjugated polymers for hybrid cellulose materials” by Joseph J. Petersonet al. published in Journal of polymer science Part A-Polymer Chemistry, 2011, 49 (14), pp 3004-3013reports grafting of poly(fluorene), poly(fluorenevinylene), and a poly(fluorene-ethynylene-phenylene) onto modified cellulose paper substrates using Suzuki,
Heck, and Sonogashira-type polymerizations, respectively. The application of these three widely used coupling chemistries to surface-grafted conjugated polymers on cellulose provides a general route to cellulose-based hybrid materials tunable with almost any aromatic repeat structure for specific applications.
Article titled “Optimization of opto-electronic property and device efficiency of polyfluorenes by tuning structure and morphology” by Peng Chen et al. published in Polymer International, 2006, 55:473-490 reports, the optimization of the opto-electronic property and device efficiency of polyfluorenes in the field of light-emitting diodes (LEDs) and photovoltaic cells (PVs) by tuning structure and morphology are summarized in terms of two typical modification techniques: copolymerization and blending. The relationships between molecular structures, thin film morphologies, opto-electronic properties and device efficiencies are discussed, and some recent progress in LEDs and PVs is simultaneously reviewed.
Article titled “Synthesis and characterization of poly(9,9-dihexylfluorene-mb-methylene)s” by James Edward Copenhafer published as thesis in 2006 reports the synthesis and characterization of copolymers possessing exact repeating sequences of 9,9-dihexylfluorene and methylene repeat units.
Article titled “All-Conjugated Diblock Copolyelectrolytes” by Andrea Gutacker, 2011 reports synthesis methods of polyfluorene.
Article titled “Simple method for the esterification of carboxylic acids” by Bernhard Neises et al. published in Angewandte Chemie, 1978, 17(7), pp 522-524 reports addition of 4-dimethylaminopyridine (DMAP) accelerates the dicyclohexylcarbo-diimide (DCC)-activated esterification of carboxylic acids to such an extent that side reactions are eliminated and even sensitive acids such 2,5-cyclohexadiene-1-carboxylic acid readily form the tert-butyl ester. DMAP has so far been used mainly as acylation catalyst.
Article titled “Molecular weight optimum in the mesoscopic order of chiral fluorene (co)polymer films” by Robert Abbel et al. published in Macromolecules, 2008, 41 (20), pp 7497-7504 reports a chiral fluorenehomopolymer (PF) and two new chiral alternating polyfluorenes, poly(fluorene-alt-benzothiadiazole) (PFBT) and poly(fluorene-alt-dithienylbenzothiadiazole) (PFDTBT), have been synthesized by palladium-catalyzed Suzuki polycondensations. In these polymers, chirality was introduced by attaching (S)-3,7-dimethyloctyl substituents to the 9-positions of the fluorene monomers. Upon thermal annealing, PF and PFBT undergo an irreversible phase transition to a liquid crystalline state that upon cooling to room temperature is vitrified and exhibits considerable circular dichroic (CD) effects. By contrast, PFDTBT forms an amorphous glass with hardly any CD activity. After fractionation by preparative size exclusion chromatography (SEC), the phase behavior of the low polydispersity polymers was studied by polarized optical microscopy (POM), differential scanning calorimetry (DSC) and CD spectroscopy. Remarkably, after fractionation also for PFDTBT a CD effect was observed and for all three materials the maximum CD effects were recorded at intermediate polymer length, indicating the presence of an optimal molecular weight for the chiral organization. In addition to the influence of molecular weight on the supramolecular organization, also annealing temperature and time, as well as film thickness were investigated.
Article titled “Experimental and theoretical evaluation of nanodiamonds as pH triggered drug carriers” by Jingjing Yan et al. published in New Journal of Chemistry, 2012,36, pp 1479-1484 reports experimental and theoretical evaluation of nanodiamonds as pH triggered drug carriers.
Article titled “Base-catalyzed reaction of fluorene and indene with lactones and hydroxy acids” by Henry E. Fritz et al. published in Journal of Organic Chemistry, 1968, 33 (6), pp 2575-2577 reports alkylation of fluorene and indene with alcohol gives 9-alkylfluorene and 1,3-dialkylidenes in high yield.
Article titled “Fluorescent nanoparticles from self-assembly of β-cyclodextrin-functionalized fluorene copolymers for organic molecule sensing and cell labeling” by Li Qun Xu et al. published in Polymer Chemistry, 2012,3, pp2444-2450 reports bromide-bearing conjugated fluorene copolymers were prepared by Suzuki coupling polymerization of 2,7-dibromo-9,9-bis(6′-bromohexyl)fluorene and 2,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,9-dihexylfluorene. Thiol-functionalized β-cyclodextrin was subsequently grafted to the bromoalkyl side chains of the fluorene copolymers via the thio-bromo ‘click’ reaction. The resulting fluorene copolymers can self-assemble into fluorescent nanoparticles surrounded by a β-cyclodextrin outer layer in an aqueous medium. Host-guest interactions of the β-cyclodextrin moieties of nanoparticles with the organic guest molecules in the aqueous medium gave rise to variations in the emission intensity of the nanoparticles.
Article titled “The α-Helix to β-Sheet transition in stretched and compressed hydrated fibrin clots” by Rustem I. Litvinov et al. published in Biophysical Journal 2012; 103(5): 1020-1027 reports Fibrin is a protein polymer that forms the viscoelastic scaffold of blood clots and thrombi. Despite the critical importance of fibrin deformability for outcomes of bleeding and thrombosis, the structural origins of the clot's elasticity and plasticity remain largely unknown. However, there is substantial evidence that unfolding of fibrin is an important part of the mechanism. We used Fourier transform infrared spectroscopy to reveal force-induced changes in the secondary structure of hydrated fibrin clots made of human blood plasma in vitro. When extended or compressed, fibrin showed a shift of absorbance intensity mainly in the amide I band (1600-1700 cm−1) as well as in the amide II and III bands, indicating an increase of the β-sheets and a corresponding reduction of the α-helices. The structural conversions correlated directly with the strain or pressure and were partially reversible at the conditions applied. The additional absorbance observed at 1612-1624 cm−1 was characteristic of the nascent interchain β-sheets, consistent with protein aggregation and fiber bundling during clot deformation observed using scanning electron microscopy. Conclude that under extension and/or compression an α-helix to β-sheet conversion of the coiled-coils occurs in the fibrin clot as a part of forced protein unfolding.
Article titled “Chiral Poly(fluorene-alt-benzothiadiazole) (PFBT) and nanocomposites with gold nanoparticles: plasmonically and structurally enhanced chirality” by Heong Sub Oh et al. published in Journal of American Chemical Society, 2010, 132 (49), pp 17346-17348 reports the plasmonic enhancement of the chiral optical activity of chiral poly(fluorene-alt-benzothiadiazole) (PFBT) doped with gold nanoparticles. The supramolecular helical organization of polymeric chains with simultaneous dipole-dipole interaction of the helically ordered nanoparticles with the polymer and one another results in unprecedented values of chirality parameter (κ˜0.02) at visible wavelengths in thin films.
Article titled “Chiroptical properties of chiral substituted Polyfluorenes” by M. Oda et al. published in Macromolecules, 2002, 35 (18), pp 6792-6798 reports liquid-crystalline polyfluorene (PF) homopolymers substituted with chiral alkyl side chains were synthesized, and their chiroptical properties in the solid state were investigated by means of circular dichroism (CD), circularly polarized photoluminescence (CPPL), and circularly polarized electroluminescence (CPEL) measurements.
Article titled “Amplification of chirality: the “Sergeants and Soldiers” principle applied to dynamic hydrogen-bonded assemblies” by Leonard J. Prins et al. published in Journal of American Chemical Society, 2001, 123 (42), pp 10153-10163 reports The amplification of supramolecular chirality has been studied in dynamic chiral hydrogen-bonded assemblies 13·(CA)6 using “Sergeants and Soldiers” experiments. Previously, it has been shown that chiral centers present in either the dimelamine component 1 or the cyanurate component CA quantitatively induce one handedness (M or P) in the assembly. This offers the possibility to study the amplification of chirality under two different kinetic regimes. When chiral dimelamines 1 are used, the exchange of chiral components and (M/P)-interconversion, i.e., interconversion between the (M)- and (P)-isomers of assembly 13·(CA)6, take place via identical pathways (condition A). When chiral cyanurates CA are used, the exchange of chiral components occurs much faster than (M/P)-interconversion (condition B). Experimentally, a much stronger chiral amplification is observed under condition B. For example, the observed chiral amplification for a mixture of chiral and achiral components (40:60) is 46% under condition B and 32% under condition A. Kinetic models were developed to fit the experimental data and to simulate chiral amplification in dynamic systems in general. These simulations show that it is theoretically possible that the diastereomeric excess in a dynamic system is more than 99% with less than 1% chiral component present.
Article titled “Polymer solutions as a pseudostationary phase for capillary electrochromatographic separation of DNA diastereomers” by Gilar M et al. published in Electrophoresis, 2000; 21(14):2999-3009 reports The solutions of linear polymers traditionally used for DNA separation have been employed for the capillary electrophoresis (CE) of diastereomers of chemically modified DNA. The selectivity of diastereomeric separation of the phosphorothioate (PS) and 2′-O-methylated (2-OMe) PS oligonucleotides depends on the nature of the polymer additive in the CE background electrolyte. The selectivity of separation for different polymers increases in the line: linear polyacrylamide<polyethylene glycol<polyvinyl pyrrolidone. The separation of oligomer diastereomers was shown to be primarily based on the hydrophobic interaction with the polymer network that acts as a pseudostationary phase. While lowering the temperature resulted in improved separation, the addition of organic modifiers such as formamide, methanol or acetonitrile counteracts the solute adsorption on the polymer network, and decreases the selectivity of DNA diastereo separation. The effect of molecular mass and concentration of the polymer on the separation selectivity was investigated.
The main drawback of a majority of these probes is their specificity to particular chemical group of analytes due to inherent specific binding nature. Besides, they require chiral isomer at high levels of enantiopurity to realize sensing activity and also for building own homochiral structure. They are thus unable to separate racemic mixture because the introduction of racemic mixture would diminish their activity.
Therefore there is need in the art to develop simple, effective and cost-effective process for the enantioselective separation of compounds. Accordingly, the present inventors developed a new polyfluorene appended with protected glutamic acid exhibiting helical porous hollow fibrous morphology for heterogeneous enantioselective separation and sensing of amino acids, amino alcohol, hydroxyl acid, sugar, aromatic drug and ascorbic acid from racemic mixture in water.